Distinct Groups Research Articles

Engineering circular bacteriocins: structural and functional effects of α-helix exchanges and disulfide introductions in circularin A.

Circular bacteriocins form a distinct group of antimicrobial peptides (AMPs) characterized by their unique head-to-tail ligated circular structure and functional properties. They belong to the ribosomally synthesized and post-translationally modified peptide (RiPP) family. The ribosomal origin of these peptides facilitates rapid diversification through mutations in the precursor genes combined with specific modification enzymes. In this study, we primarily explored the bacteriocin engineering potential of circularin A, a circular bacteriocin produced by Clostridium beijerinckii ATCC 25752. Specifically, we employed strategies involving α-helix replacements and disulfide bond introductions to investigate their effects on both biosynthesis and bioactivity of the bacteriocin. The results show the feasibility of peptide engineering to introduce certain structural properties into circularin A through carefully designed approaches. The introduction of cysteines for potential disulfide bonds resulted in a substantial reduction in bacteriocin biosynthesis and/or bioactivity, indicating the importance of maintaining dynamic flexibility of α-helices in circularin A, while reduction of the potential disulfide in one case increased the activity. The 5 α-helices of circularin A were respectively replaced by corresponding helices from another circular peptide, enterocin AS-48, and modestly active peptides were obtained in a few cases. Overall, this study provides valuable insights into the engineering potential of circular bacteriocins as antimicrobial agents, including their structural and functional restrictions and their suitability as peptide engineering scaffolds. This helps to pave the way for the development of novel antimicrobial peptides with tailored properties based on circular bacteriocins.

The effects of eccentric training on hamstring flexibility and strength in young dance students

The objective of this research is to examine the impact of eccentric training on hamstring flexibility and strength in young dancers during the concluding stages of their foundational dance training program. A total of 24 female, second-year dance students from Hebei Normal University were selected as participants. They were divided into three distinct groups: Nordic hamstring exercise and single-leg deadlift group (NHE&SLD), forward bending exercises and standing leg lift group (FBE&SLL), and a control group (CG). The study was designed around a 6-week training regimen. An isokinetic dynamometer was used to measure seated knee flexor–extensor strength, while electronic goniometry was employed to measure hamstring flexibility in the supine position. Paired sample t-tests were conducted within each group, and one-way analysis of covariance (ANCOVA) was utilized for comparisons between groups. In the NHE&SLD group, significant disparities were observed in both concentric (T = − 5.687, P = 0.001) and eccentric (T = − 3.626, P = 0.008) hamstring strength pre and post-intervention. The pre-intervention dominant leg concentric strength test values significantly influenced the post-intervention outcomes (F = 5.313, P = 0.001, η2 = 0.840). Similarly, the pre-intervention dominant leg eccentric strength test values impacted the post-intervention results (F = 4.689, P = 0.043, η2 = 0.190). Following the intervention, the NHE&SLD group displayed marked changes in the active straight leg raising angle on both left (T = − 4.171, P = 0.004) and right (T = − 6.328, P = 0.001) sides. The FBE&SLL group also revealed significant changes in the active straight leg raising angle on both left (T = − 4.506, P = 0.003) and right (T = − 4.633, P = 0.002) sides following the intervention. The pre-intervention left leg concentric strength test value significantly influenced the post-intervention outcomes (F = 25.067, P = 0.001, η2 = 0.556). Likewise, the pre-intervention right leg eccentric strength test value significantly influenced the post-intervention results (F = 85.338, P = 0.01, η2 = 0.810). Eccentric training can better enhance the flexibility and strength of hamstring muscles in dance students. Traditional stretching training significantly improves the flexibility of the hamstring muscles. Eccentric training has more training benefits than traditional stretching training. It is recommended for dance students to use eccentric training when increasing hamstring flexibility and strength.

Bridging gaps: Transforming dental public health training for modern job market demands.

To create optimal oral and overall community health, dental public health (DPH) specialists must be competent and appropriately skilled to deal with contemporary and emergent public health issues. This study aims to evaluate the current job market demands related to the DPH profession and suggest contemporary skills and qualities that would enable DPH professionals to address emerging issues more effectively in their field. A multimethod qualitative study was conducted involving two distinct groups: employers and potential employees. Interviews of stakeholders (employers)representing different job market domains, and a surveywas administered to recent DPH residency graduates (employees). Qualitative analysis was applied to the data collected. Employers identified the following skills as crucial for future DPH employees: proficiency in care delivery systems, health informatics, clinical training, leadership, and professional and grant writing skills. Many employers assumed the presence of a clinical component in the residency program. DPH residency graduates emphasized that the most significant barrier to securing positions is the lack of clinical experience within the residency program. This research highlights skills currently valued by the DPH job market and proposes that DPH specialty training may consider revising its curriculum to include these skills. Implementing such updates would ensure that graduates are well equipped and competitive, thus significantly contributing to the broader objective of attaining optimal oral health and overall well-being of the community.

Association of Functional Status and Symptom Severity Among Patients Who Received Palliative Care Consultations.

Background: The relationship between functional status and the severity of different symptoms in patients with serious illnesses has not been explored in detail. Methods: We retrospectively evaluated registry data of hospitalized patients who received inpatient palliative care consults at the Mount Sinai Health System between January 01, 2020, and December 31, 2022. The registry was approved by the local institutional review board. During the initial consult, palliative care clinicians administered the Australia-modified Karnofsky Performance Status (KPS) and the Edmonton Symptom Assessment System (ESAS). We extracted these measures and other variables of interest from electronic health records and billing data, and assessed the association of functional status and symptom severity for different symptoms using ordinal logistic regression models. Results: The study included 9800 patients who received a palliative care consult. When modeling the association of functional status and the severity of different symptoms, two distinct groups of symptoms emerged: Nausea, physical discomfort, anxiety, depression, and constipation were more prevalent and severe among patients with higher functional status. Conversely, drowsiness, inactivity, dyspnea, anorexia, and agitation were more prevalent and severe among patients with lower functional status. These findings remained statistically significant after adjusting for possible confounders. Conclusion: Among patients who received inpatient palliative care consults, lower functional status was associated with a higher symptom burden. Furthermore, symptom profiles differed between patients with reduced functional status and those with preserved functional status.

Association between visceral fat area and diabetic retinopathy among people with type 2 diabetes mellitus: a cross-sectional study in Ningbo, Zhejiang Province, China.

The objective of this study is to investigate the relationship between visceral fat area (VFA) and diabetic retinopathy (DR) in the context of type 2 diabetes mellitus (T2DM) within Ningbo, China. The data of a total of 3,707 subjects with T2DM treated at The First Affiliated Hospital of Ningbo University were enrolled. The existence and severity of diabetic retinopathy were assessed by employing the 45° two-field stereoscopic digital photography. Subjects were categorized into four distinct groups: those without DR (NDR), individuals with mild non-proliferative DR (mild NPDR), people with moderate non-proliferative DR (moderate NPDR), and those suffering from vision-threatening DR (VTDR). Bio-electrical impedance was employed to estimate the Visceral fat area (VFA). Multinomial logistic regression models were utilized to evaluate the association between VFA and DR. The mean VFA in patients without diabetic retinopathy (NDR) was notably lower compared to that of patients with diabetic retinopathy (DR) (85.21 ± 37.78 vs. 97.37 ± 44.58 cm2, p < 0.001). As the severity of DR increased, VFA increased gradually but insignificantly (94.41 ± 43.13 cm2, 96.75 ± 40.82 cm2, 100.84 ± 49.34 cm2, p = 0.294). After adjusting the confounding factors, there was an association identified between VFA and the occurrence of DR (OR = 1.020, 95% CI = 1.016-1.024). It showed that regardless of BMI, whether it's less than 25 kg/m2 or greater than or equal to 25 kg/m2, a higher VFA (≥100 cm2) level came with a higher prevalence of DR (p < 0.001). The outcomes of this research indicate a modest association between VFA and the incidence of DR among Chinese patients who have been diagnosed with T2DM in Ningbo.

Maintaining an Aberrant Practice in a Contradictory Environment: The Case of Doping in Professional Road Cycling

AbstractSports doping is a practice that continues, despite hostile public opinion and counter‐efforts to close it down. In this paper we explore the maintenance of doping in the sport of professional road cycling. While studies of controversial practices find that they often benefit from levels of acceptance and even perceived value, we supplement such research by providing one of the few studies of practices that are subject to powerful social controls. In our case, the continual threat from anti‐doping organizations means that the maintenance and disruption of doping represents a kind of dialectical pair. We utilize and extend a model of types of institutional work that has advantages as an analytical tool, exploring the support required in this setting. Sustaining work was highly dynamic, relying on distinct groups within cycling teams to marshal organizational skills and cope with disruption, while repairing internal defences and concealing activities.

Pairing relations within CO3 chondrites recovered at the Dominion Range and Miller Range, Transantarctic mountains: Constraints from chondrule olivines, noble gas, and H, C, N bulk and isotopic compositions

AbstractThe Dominion Range (DOM) and Miller Range (MIL) dense collection areas (DCAs) have yielded more than 20 and 200 CO3 chondrites (carbonaceous chondrites of the Ornans chemical group), respectively, over multiple field seasons. Several samples have exhibited primitive characteristics and have been the focus of interest. With so many CO3s recovered from this area, a natural question is if there are multiple pairing groups (where pairing refers to two or more meteorites that are part of a single fall) and if there is additional primitive material that would interest the meteorite community. This comprehensive study looks at all samples using several approaches: field and macroscopic observations; magnetic susceptibility; Cr in ferroan olivine; bulk elemental and isotopic analysis of H, C, N, and noble gas analyses to determine cosmic ray exposure (CRE) ages. Magnetic susceptibilities (measured as logχ) for all samples correlate with their type II (i.e., FeO‐rich) olivine Cr contents, with the most primitive CO3s (3.00) have logχ values near 5, while the higher grade CO3s have logχ values as low as 4.17. Altogether, there appear to be two distinct CO3 pairing groups and five other unpaired CO3s recovered at the Dominion Range: (a) the main DOM 08004 pairing group (16 specimens with a CRE age of 10–16 Ma), (b) the DOM 08006 group (2 specimens incl. DOM 10847 with a CRE age of 25 Ma), (c) DOM 14359 with a CRE age of 6 Ma, (d) DOM 18070 with a CRE age of 8 Ma (these two samples have similar ages but distinct trapped 20Ne contents), (e) DOM 10900 with a CRE age of 5.5 Ma, (f) DOM 18286 (with a CRE age of ~59 Ma), and (g) DOM 19034 (with a CRE age of ~43 Ma). There are three distinct age groupings of 3.00–3.05 COs, highlighting the diverse pristine CO3 materials present in the DOM area. There is one large MIL pairing group (MIL 07099; n = 199; 9–14 Ma CRE age where measured) and one smaller pairing group with distinctly lower Cr2O3 in type II olivines (8 samples of unknown CRE age), and five unpaired or unique CO3s. Notably, the large DOM and MIL pairing groups have 9–16 Ma exposure ages that could have been delivered in a single large fall event spanning ~200 km, two separate falls that were ejection paired, or two separate falls from two separate ejections. Finally, we recommend reclassifying several CO3 to CM2 based on new data and that from previous studies.

Kidney scoring surveillance: predictive machine learning models for clear cell renal cell carcinoma growth using MRI.

Classification of clear cell renal cell carcinoma (ccRCC) growth rates in patients with Von Hippel-Lindau (VHL) syndrome has several ramifications for tumor monitoring and surgical planning. Using two separate machine-learning algorithms, we sought to produce models to predict ccRCC growth rate classes based on qualitative MRI-derived characteristics. We used a prospectively maintained database of patients with VHL who underwent surgical resection for ccRCC between January 2015 and June 2022. We employed a threshold growth rate of 0.5cm per year to categorize ccRCC tumors into two distinct groups-'slow-growing' and 'fast-growing'. Utilizing a questionnaire of qualitative imaging features, two radiologists assessed each lesion on different MRI sequences. Two machine-learning models, a stacked ensemble technique and a decision tree algorithm, were used to predict the tumor growth rate classes. Positive predictive value (PPV), sensitivity, and F1-score were used to evaluate the performance of the models. This study comprises 55 patients with VHL with 128 ccRCC tumors. Patients' median age was 48years, and 28 patients were males. Each patient had an average of two tumors, with a median size of 2.1cm and a median growth rate of 0.35cm/year. The overall performance of the stacked and DT model had 0.77 ± 0.05 and 0.71 ± 0.06 accuracies, respectively. The best stacked model achieved a PPV of 0.92, a sensitivity of 0.91, and an F1-score of 0.90. This study provides valuable insight into the potential of machine-learning analysis for the determination of renal tumor growth rate in patients with VHL. This finding could be utilized as an assistive tool for the individualized screening and follow-up of this population.

Extracting latently overlapping users by graph neural network for non-overlapping cross-domain recommendation

Cross-domain collaborative filtering (CDCF) is an effective solution to alleviate the data sparsity problem. Most of existing CDCF methods rely on overlapping data, such as users, items or both. But in some realistic scenes, detection and accessibility of overlapping data are difficult or even impossible, which poses a pressing demand for researches on cross-domain recommendation without overlapping data. There actually have been some attempts on addressing this problem by sharing cluster-level rating pattern across source and target domains. But these solutions require explicit ratings, which makes them not suitable for more common implicit feedback recommendation. To address this problem, we propose a novel CDCF model for non-overlapping data scenarios, which adaptively extracts latently overlapping users of source and target domains from all users to build an implicit bridge for knowledge transfer. Specifically, we first design a self-supervised classifier guided by inter-domain contrastive learning to divide domain users into distinct groups based on their preference differences. Then, we perform graph convolution operations on the subgraph formed by such group users and their interactive items to explicitly mine the higher-order collaborative relationships between users and items. Finally, we construct sparse and reasonable implicit bridges between domains by designing flow-aware similarity measures for selective knowledge transfer among the extracted latently overlapping users. Extensive experiments on four public datasets demonstrate the superior performance of our proposed model over several state-of-the-art graph-based single- and cross-domain models.

Subjective long-term emotional and social effects of recreational MDMA use: the role of setting and intentions

MDMA is a recreational drug commonly used to enhance euphoria, but it is also used in non-party settings with self-insight or social connection intentions. Yet, little is known about whether distinct consumer groups are formed based on consumption setting and intention. We aimed to characterize different types of recreational MDMA users based on consumption setting and intentions, and to examine their differences in perceptions of long-term social-emotional effects of MDMA use. We analyzed self-reports of 766 individuals (ages 18–61, mostly from Western countries), reporting on their MDMA consumption habits and perceived effects. We used a K-medoids clustering algorithm to identify distinct types of consumption settings and intentions. We identified three setting types – party settings with friends (N = 388), private home settings (N = 132), mixed settings (N = 246) – and three intention types – euphoria and energy (N = 302), self-insight (N = 219), mixed intentions (N = 245). Members of the self-insight and mixed intentions clusters reported considerably more long-term socio-emotional benefits than members of the euphoria and energy cluster. No differences were observed between the setting clusters. In this particular sample, more long-term benefits than harms were reported. Our findings suggest that the long-term social-emotional benefits of MDMA are associated with whether users seek self-insight or have mixed intentions.

Biosynthesis of the Azoxy Compound Azodyrecin from Streptomyces mirabilis P8-A2.

Azoxy compounds are a distinctive group of bioactive secondary metabolites characterized by a unique RN═N+(O-)R moiety. The azoxy moiety is present in various classes of metabolites that exhibit various biological activities. The enzymatic mechanisms underlying azoxy bond formation remain enigmatic. Azodyrecins are cytotoxic azoxy metabolites produced by Streptomyces mirabilis P8-A2. Here, we cloned and confirmed the putative azd biosynthetic gene cluster through CATCH cloning followed by expression and production of azodyrecins in two heterologous hosts, S. albidoflavus J1074 and S. coelicolor M1146, respectively. We explored the function of 14 enzymes in azodyrecin biosynthesis through gene knockout using CRISPR-Cas9 base editing in the native producer, S. mirabilis P8-A2. The key intermediates were analyzed in the mutants through MS/MS fragmentation studies, revealing azoxy bond formation via the conversion of hydrazine to an azo compound followed by further oxygenation. Enzymes involved in modifications of the precursor could be postulated based on their predicted function and the intermediates identified in the knockout strains. Moreover, the distribution of the azoxy biosynthetic gene clusters across Streptomyces spp. genomes is explored, highlighting the presence of these clusters in over 20% of the Streptomyces spp. genomes and revealing that azoxymycin and valanimycin are scarce, while azodyrecin and KA57A-like clusters are widely distributed across the phylogenetic tree.

A multi‐analytical approach applied to pottery from Oman as a key to understanding ancient Indian Ocean maritime trade

AbstractThe populations in Sumhuram (third/second century bce to fifth century ce) and Hamr al‐Sharqiya 1 (HAS1) (first millennium bce to first/second century ce) were involved in one of the most important examples of large‐scale trade systems in antiquity: the maritime network connecting the coasts of the Indian Ocean. This research focuses on a total of 35 southwestern Arabian and Indian pottery sherds from both the settlements of Sumhuram and Hamr al‐Sharqiya 1, analysed through a multi‐analytical complementary approach. This study intends to test the input potential of this type of approach applied to ceramics in the context of the Indian Ocean trade network. The techniques adopted are powder X‐ray diffraction, optical microscopy, inductively coupled plasma–mass spectrometry and scanning electron microscopy coupled with energy‐dispersive X‐ray spectroscopy. The results obtained allow the identification of eight distinct groups, each characterized by unique (textural, mineralogical, geochemical) signatures, providing specific clues for determining their provenance, specifically from the Indian subcontinent and southwestern Arabia. This paper shows the importance of this type of archaeometric study that must be integrated into a transdisciplinary approach.

IDH mutation, glioma immunogenicity, and therapeutic challenge of primary mismatch repair deficient IDH‐mutant astrocytoma PMMRDIA: a systematic review

In 2021, Suwala et al. described Primary Mismatch Repair Deficient IDH‐mutant Astrocytoma (PMMRDIA) as a distinct group of gliomas. In unsupervised clustering, PMMRDIA forms distinct cluster, separate from other IDH‐mutant gliomas, including IDH‐mutant gliomas with secondary mismatch repair (MMR) deficiency. In the published cohort, three patients received treatment with an immune checkpoint blocker (ICB), yet none exhibited a response, which aligns with existing knowledge about the decreased immunogenicity of IDH‐mutant gliomas in comparison to IDH‐wildtype. In the case of PMMRDIA, the inherent resistance to the standard‐of‐care temozolomide caused by MMR deficiency is an additional challenge. It is known that a gain‐of‐function mutation of IDH1/2 genes produces the oncometabolite R‐2‐hydroxyglutarate (R‐2‐HG), which increases DNA and histone methylation contributing to the characteristic glioma‐associated CpG island methylator phenotype (G‐CIMP). While other factors could be involved in remodeling the tumor microenvironment (TME) of IDH‐mutant gliomas, this systematic review emphasizes the role of R‐2‐HG and the subsequent G‐CIMP in immune suppression. This highlights a potential actionable pathway to enhance the response of ICB, which might be relevant for addressing the unmet therapeutic challenge of PMMRDIA.

Prevalence, lived experiences and user profiles in e-cigarette use: A mixed methods study among French college students.

Little is known about e-cigarette use in French students. Our aims were to estimate the prevalence of e-cigarette experimentation and current e-cigarette use; describe the reasons for using e-cigarettes; explore the vaping experience and identify the profiles of e-cigarette users. We used a sequential, explanatory mixed methods design in a sample of French college students. Quantitative data was collected online for a cross-sectional analysis among 1698 students. Two separate analysis based on the thematic analysis and the Grounded Theory were also performed in 20 semi-structured interviews, focusing former and current smokers also current vapers. The prevalence of e-cigarette experimentation was 39.3% (95% CI: 35.2-44.0) and 5.1% (95% CI: 3.2-8.0) of students were current e-cigarette users. Experimentation was opportunistic while current usage was rational, requiring to acquire a personal electronic device, getting used to its technicality, appreciating its availability, discretion, and learning the practice. In this context, three distinct groups of e-cigarette users were identified, based on assumed identity, tobacco and e-cigarette use, the functions assigned to e-cigarettes, and intentions with regards to vaping in the future. Despite some limitations mainly related to the participants self-selection, this research showed that while many smokers and former smokers have tried e-cigarettes in this student population, few have continued to use them continuously. Moreover, these current e-cigarette users were a heterogeneous group. Longitudinal studies are needed in young adult smokers for a better understanding of how their tobacco and e-cigarette use affect each other and change over time.

Job Satisfaction within the Grassroots Healthcare System in Vietnam's Key Industrial Region-Binh Duong Province: Validating the Vietnamese Version of the Minnesota Satisfaction Questionnaire Scale.

Background: The grassroots healthcare system is the closest and most community-oriented force, working as an extended arm of the primary healthcare network to implement healthcare programs at the household level. Its comprehensive development is a crucial task set by the Vietnamese government. Job satisfaction significantly influences the performance of healthcare staff within this system. Objective: to assess job satisfaction among healthcare staff using the short-form of the Minnesota Satisfaction Questionnaire while also evaluating the Vietnamese translation of this scale. Methods: A descriptive cross-sectional study with analysis based on the responses of 587 healthcare staff using the Vietnamese-translated version of the MSQ short-form scale. The response data from the participants were subjected to CFA, and if the proposed CFA model did not fit the data, EFA was conducted. Results: The results indicate that the new model, which evaluates job-related factors in three distinct groups, is more suitable than the original model. The 14 questions of the MSQ scale were analyzed and categorized into Autonomy, Obligation, and Specificity based on the participants' responses. The confirmatory factor analysis (CFA) conducted on the new model demonstrated favorable fit indices: CFI = 0.934, TLI = 0.917, GFI = 0.919, and RMSEA = 0.093 (90% CI: 0.085-0.102). Conclusions: The Vietnamese version of the MSQ short form demonstrates reliability and validity. It also provides additional data on the effectiveness of the MSQ short form in measuring job satisfaction.

Detection of Salmonella Typhi bacteriophages in surface waters as a scalable approach to environmental surveillance.

Environmental surveillance, using detection of Salmonella Typhi DNA, has emerged as a potentially useful tool to identify typhoid-endemic settings; however, it is relatively costly and requires molecular diagnostic capacity. We sought to determine whether S. Typhi bacteriophages are abundant in water sources in a typhoid-endemic setting, using low-cost assays. We collected drinking and surface water samples from urban, peri-urban and rural areas in 4 regions of Nepal. We performed a double agar overlay with S. Typhi to assess the presence of bacteriophages. We isolated and tested phages against multiple strains to assess their host range. We performed whole genome sequencing of isolated phages, and generated phylogenies using conserved genes. S. Typhi-specific bacteriophages were detected in 54.9% (198/361) of river and 6.3% (1/16) drinking water samples from the Kathmandu Valley and Kavrepalanchok. Water samples collected within or downstream of population-dense areas were more likely to be positive (72.6%, 193/266) than those collected upstream from population centers (5.3%, 5/95) (p=0.005). In urban Biratnagar and rural Dolakha, where typhoid incidence is low, only 6.7% (1/15, Biratnagar) and 0% (0/16, Dolakha) river water samples contained phages. All S. Typhi phages were unable to infect other Salmonella and non-Salmonella strains, nor a Vi-knockout S. Typhi strain. Representative strains from S. Typhi lineages were variably susceptible to the isolated phages. Phylogenetic analysis showed that S. Typhi phages belonged to the class Caudoviricetes and clustered in three distinct groups. S. Typhi bacteriophages were highly abundant in surface waters of typhoid-endemic communities but rarely detected in low typhoid burden communities. Bacteriophages recovered were specific for S. Typhi and required Vi polysaccharide for infection. Screening small volumes of water with simple, low-cost (~$2) plaque assays enables detection of S. Typhi phages and should be further evaluated as a scalable tool for typhoid environmental surveillance.

A novel anoikis-related gene signature identifies LYPD1 as a novel therapy target for bladder cancer

Bladder cancer (BLCA) is a malignant tumor associated with unfavorable outcomes. Studies suggest that anoikis plays a crucial role in tumor progression and cancer cell metastasis. However, its specific role in bladder cancer remains poorly understood. Our objective was to identify anoikis-related genes (ARGs) and subsequently construct a risk model to assess their potential for predicting the prognosis of bladder cancer.The transcriptome data and clinical data of BLCA patients were sourced from The Cancer Genome Atlas and GEO database. We then performed the differential expression analysis to screen differentially expressed ARGs. Subsequently, we conducted non-negative matrix factorization (NMF) clustering analysis to establish molecular subtypes based on the differentially expressed ARGs. The CIBERSORT algorithm was used to estimate the quantification of different cell infiltration in BLCA tumor microenviroment. A prognostic risk model containing 7 ARGs was established using Lasso-Cox regression analysis. The nomogram was built for predicting the survival probability of BLCA patients. To determine the drug sensitivity of each sample from the high- and low-risk groups, the R package “pRRophetic” was performed. Finally, the role of LYPD1 was explored in BLCA cell lines.We identified 90 differential expression ARGs and NMF clustering categorizated the BLCA patientss into two distinct groups (cluster A and B). Patients in cluster A had a better prognosis than those in cluster B. Then, we established a ARGs risk model including CALR, FASN, FOSL1, JUN, LYPD1, MST1R, and SATB1, which was validated in the train and test set. The results suggested overall survival rate was much higher in low risk group than high risk group. The cox regression analysis, ROC curve analysis, and nomogram collectively demonstrated that the risk model served as an independent prognostic factor. The high risk group had a higher level TME scores compared to the low risk group. Furthermore, LYPD1 was low expression in BLCA cells and overexpression of LYPD1 inhibits the prolifearation, migration and invasion.In the current study, we have identified differential expression ARGs and constructed a risk model with the promise for guiding prognostic predictions and provided a therapeutic target for patients with BLCA.

Effect of magnesium oxide nanoparticles and LED irradiation on the viability and differentiation of human stem cells of the apical papilla.

Currently, regenerative endodontic treatments are gaining more and more attention, and stem cells play a significant role in these treatments. In order to enhance stem cell proliferation and differentiation, a variety of methods and materials have been used. The purpose of this study was to determine the effects of magnesium oxide nanoparticles and LED irradiation on the survival and differentiation of human stem cells from apical papilla. The MTT test was used to measure the cell survival of SCAPs that had been exposed to different concentrations of magnesium oxide nanoparticles after 24 and 48h, and the concentration with the highest cell survival rate was picked for further studies. The cells were classified into four distinct groups based on their treatment: (1) control, which received no exposure, (2) exposure to magnesium oxide nanoparticles, (3) exposure to light emitting diode (LED) irradiation (635nm, 200mW/cm2) for 30s, (4) exposure simultaneously with magnesium oxide nanoparticles and LED irradiation. A green approach was employed to synthesize magnesium oxide nanoparticles. Quantitative real time PCR was used to measure the gene expression of osteo/odontogenic markers such as BSP, DSPP, ALP and DMP1 in all four groups after treatment, and Alizarin red S staining (ARS) was used to determine the osteogenic differentiation of SCAPs by demonstrating the Matrix mineralization. The highest viability of SCAPs was observed after 24h in concentration 1 and 10µg/mL and after 48h in concentration 1µg/mL, which were not significantly different from the control group. In both times, the survival of SCAPs decreased with increasing concentration of magnesium oxide nanoparticles (MgONPs). According to the results of Real-time PCR, after 24 and 48h, the highest differentiation of BSP, DMP1, ALP and DSPP genes was observed in the LED + MgONPs group, followed by MgONPs and then LED, and in all 3 experimental groups, it was significantly higher than control group (P < 0.05). Also, after 24 and 48h, the density of ARS increased in all groups compared to the control group, and the highest density was observed in the MgONPs + LED and MgONPs groups. This research concluded that exposure to SCAPs, MgONPs, and LED irradiation has a significant effect on enhancing gene expression of odontogenic/osteogenic markers and increasing matrix mineralization.

Preferences for risks and benefits of treatment outcomes for chronic low back pain: Choice-based conjoint measure development and discrete choice experiment.

Understanding individual patient preferences for chronic low back pain (cLBP) outcomes is essential for targeting available therapeutic options; yet tools to elicit patient outcome preferences are limited. To develop and test a choice-based conjoint (CBC) measure, commonly used in behavioral economics research, to elicit what outcomes patients with cLBP want to achieve and avoid. We developed a survey-based CBC measure to allow patients to make risk/benefit trade-off choices between possible treatment outcomes. After extensive literature, clinician, and patient input, our measure included seven attributes: fatigue, anxiety/depression, difficulty thinking/making decisions, pain intensity, physical abilities, change in pain, and ability to enjoy life despite pain. Random-parameters logit models were used to estimate strength of preferences, and latent class analysis was used to identify patient characteristics associated with distinct preference. Online study using the Sawtooth web-based platform. Two hundred eleven individuals with cLBP recruited from online advertising as well as at clinical sites across multiple academic and private institutions. Not applicable. The most valued outcome was the highest level of physical activity (β = 1.6-1.98; p < .001), followed by avoiding cognitive difficulties (β = -1.48; p < .001). Avoidance of severe pain was comparable to avoiding constant fatigue and near-constant depression/anxiety (β = -0.99, -1.02); p < .001). There was an association between preferences and current pain/disability status; patients with higher pain had a stronger preference to avoid severe pain, whereas those with higher disability have stronger preferences for achieving physical activity. The latent class analysis identified two distinct groups: (1) more risk-seeking and willing to accept worse outcomes (56%); and (2) more risk-averse with a stronger preference for achieving maximum benefits (44%). Our study illuminated cLBP patient preferences for treatment outcomes and heterogeneity in these preferences. Patients stressed the importance of reaching high physical activity and avoiding cognitive declines, even over a desire to avoid pain. More work is needed to understand patient preferences to aid informed, shared decisions.

Morphological Characterization and Diversity Assessment of Mungbean [Vigna radiata (L.) Wilczek] Genotypes using DUS Descriptors as per PPV and FRA, 2001

Background: Variety characterization is the foremost important step that should be done by breeders to classify a variety into distinct groups. A significant technique for locating and assessing several genotypes for the registration, protection and production of seeds of superior quality is the Distinctness, Uniformity and Stability (DUS) characterization. Consequently, the current investigation aimed to use DUS descriptors to describe and assess the variance present in mungbean genotypes. Methods: One hundred forty-two mungbean genotypes were examined using 21 agro-morphological qualitative DUS descriptors in a randomized block design with two replications across two seasons, kharif 2021 and kharif 2022. Result: In the twenty-one DUS traits that were examined, four characters’ plant growth habit, leaf shape, leaf size and seed size exhibited trimorphic variance. Three characters (plant habit, stem pubescence and pod pubescence) were found to be identical among all genotypes while fourteen characters displayed dimorphic variance. All of the mungbean genotypes displayed a significant degree of variance for all DUS characteristics. Based on the UPGMA method of clustering, the dendrogram classified all the one hundred forty-two genotypes into three major clusters. The presence of variation among the genotypes under study was demonstrated by the further classification of these primary clusters into five sub-clusters. The majority of the genotypes were found in cluster II (121 genotypes), which was followed by cluster I (18 genotypes) and cluster III (3 genotypes).